Vitamin U prevents valproic acid-induced liver injury through supporting enzymatic antioxidant system and increasing hepatocyte proliferation triggered by inflammation and apoptosis

Celik E., Tunali S., Gezginci-Oktayoglu S., BOLKENT Ş., Can A., Yanardag R.

TOXICOLOGY MECHANISMS AND METHODS, cilt.31, sa.8, ss.600-608, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31 Sayı: 8
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1080/15376516.2021.1943089
  • Dergi Adı: TOXICOLOGY MECHANISMS AND METHODS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.600-608
  • Anahtar Kelimeler: Vitamin U, valproic acid, liver injury, antioxidant system, apoptosis, proliferation, OXIDATIVE STRESS, INDUCED HEPATOTOXICITY, REGENERATION, METABOLISM, CASPASES, REPAIR
  • İstanbul Üniversitesi Adresli: Evet

Özet

The aim of this study was to investigate the cellular mechanisms that cause valproic acid (VPA)-induced liver damage and the therapeutic effect of Vitamin U (Vit U) on these mechanisms. Female Sprague Dawley rats were randomly divided into four groups: intact control animals, animals that received Vit U (50 mg/kg/day), animals given VPA (500 mg/kg/day), and animals given both VPA and Vit U. The rats in the Vit U + VPA group were administered Vit U by gavage an hour before VPA administration every day for 15 days. Liver tissues were evaluated through histopathological, biochemical, immunohistochemical, and Western blotting techniques. Administration of Vit U with VPA resulted in (i) prevention of histopathological changes caused by VPA; (ii) blockage of the decrease in catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities; prevention of the elevation in gamma-glutamyl transferase (GGT) activity and advanced oxidation protein products (AOPP) level; (iii) increased in the levels of interleukin-1 beta (IL-1 beta), active caspase-3, and cytoplasmic cytochrome c; (iv) increase in cleaved poly (ADP-ribose) polymerase (PARP) level and decrease in LC3B (II/I) ratio; (v) increase in the number of proliferating cells nuclear antigen (PCNA) positive hepatocytes. These findings show that Vit U prevents liver damage caused by VPA through increasing the antioxidant enzyme capacity and hepatocyte proliferation by triggering inflammation and apoptosis. These findings suggest that Vit U provides its protective effects against VPA-induced liver damage by stimulating homeostasis and regeneration.